Inorganic materials such as bioactive glasses and composites are used in dental applications but suffer from a number of drawbacks including brittleness, mismatch in mechanical properties with surrounding tissues and poor interfacial stability. In the present proposal we describe a novel biomimetic nanocomposite approach to address these limitations. Importantly, we exploit two critical lessons in materials science and engineering from Nature, nanoscale protein structures and control of organic-inorganic interfaces, to optimize material features. We describe new biomaterial nanocomposites formed from bioengineered fusion proteins that consist of two components: (a) a protein self-assembling domain based on mimicking the consensus repeat in spider dragline silk - due to the formation of highly stable (beta-sheet) secondary structures with impressive mechanical properties, and (b) a silica-forming domain derived from the silicatin protein of a diatom that offers versatility in control of the reactions that generate silica and different morphologies. These fusion proteins provide a novel approach to nanoscale materials assembly and control, leading to well-organized composite material structures that can be formed either in vitro (prior to implantation) or in vivo (conformal fill ins, interfacial bonding, avoid shrinkage due to the composite features) in biocompatible approaches. The hypothesis for the proposed study is that nanocomposite material features (structure, morphology, mechanical) can be optimized and controlled (at different length scales) through appropriate design of chimeric (fusion) proteins in which the self-assembling structural domains and functional (silica forming) domains are linked at the molecular level. Our goal is to elucidate how alterations in the chemistry of the two domains will lead to predictable changes in composite material properties (structure, morphology, mechanics) (Aim #1), to optimize features for in situ materials formation based on biocompatible reaction conditions (Aim #2), and to assess the new materials for dentinogenic restoration in vitro and in vivo (Aim #3). Our preliminary data demonstrate the feasibility of the proposed approach and offers a new platform for in situ silica formation with unprecedented control of materials design and functional properties. The silica-forming domain can also be further modified to form other inorganic phases (e.g., hydroxyapatite, titanium dioxide), thus the versatility and opportunities that can be explored with this chimeric biomimetic protein design strategy are expansive. [unreadable] [unreadable] [unreadable]